Triple Therapy (LABA/LAMA/ICS) vs LABA/LAMA Combo for COPD

Sarfaroj Khan 


October 23, 2020


  • In patients with chronic obstructive pulmonary disease (COPD), triple therapy (long-acting beta-adrenoceptor agonists [LABA]/long-acting muscarinic antagonists [LAMA]/inhaled corticosteroid [ICS]) was more effective in reducing moderate-to-severe exacerbations and mortality than LABA/LAMA combination.

  • However, the risk of pneumonia was increased with triple therapy vs LABA/LAMA combination.

Why this matters

  • Findings highlight the need for more prospective trials to address the risk/benefit of triple therapy to understand the characteristics of patient subgroups who may benefit from triple therapy and those for whom the extra risk of adverse events may outweigh any benefits.

Study design

  • 231 studies (212 randomised controlled trials [RCTs] and 19 observational studies; n=255,857) met eligibility criteria after a search on MEDLINE, EMBASE and the Cochrane Library.

  • Funding: Boehringer Ingelheim Ltd.

Key results

  • Compared with LABA/LAMA combination, triple therapy (LABA/LAMA/ICS) was more effective in reducing:

    • exacerbations (long-term: ≥20 weeks of treatment; HR, 0.85; 95% CI, 0.78-0.94; short-term: <20 weeks; HR, 0.67; 95% CI, 0.49-0.9); and

    • mortality (HR, 0.72; 95% CI, 0.59-0.89).

  • The risk of pneumonia was increased with triple therapy vs LABA/LAMA combination (HR, 1.35; 95% CI, 1.10-1.67).

  • No differences were observed between the groups in:

    • lung function (mean difference [MD], 0.02; 95% CI, −0.10 to 0.14);

    • health-related quality of life (MD, −1.12; 95% CI, −3.83 to 1.59); and

    • adverse events (MD, 1.02; 95% CI, 0.96-1.08).

  • Most of the observational evidence trended in the same direction as pooled RCT data.


  • Risk of bias.


Axson EL, Lewis A, Potts J, Pang M, Dickinson S, Vioix H, Quint JK. Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis. BMJ Open. 2020;10(9):e036455. doi: 10.1136/bmjopen-2019-036455. PMID: 32994234 View full text

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: